Speaker

Deborah J. Nelson

University of Chicago

Neurobiology, Pharmacology and Physiology

773-702-0126

nelson@uchicago.edu

Human Disease Associated with Defects in Membrane Ion Channels

Bacterial infections are the major cause of death in patients with cystic fibrosis. The immune system fights bacterial infection primarily through the activity of the macrophage, a mobile cell type capable of recognizing, engulfing, and killing foreign particles including bacteria encountered throughout the body. In the lung, the macrophage forms the first line of defense against pathogens that enter the body through the airways. In addition, macrophages secrete a number of signaling molecules that recruit other cell types within the immune system to sites of infection. We have determined that the CF transmembrane regulator (CFTR), the protein that is defective in the disease, is also expressed in the macrophage and its function appears to control the manner in which molecules important to immune system activation are released by the macrophage. Our studies will allow us to determine whether the absence or dysfunction of CFTR leads to a decrease in the ability of the lung macrophage to fight bacterial infection. We will determine whether CFTR controls the ability of the macrophage to take up infectious bacteria, whether it controls the secretion of molecules that recruit other cell types in the immune system to fight infection, or whether both of these functions are controlled by the protein. These studies will allow us to determine whether the molecular basis for the susceptibility of CF patients to lung infections involves loss of macrophage function as a result of a loss of function of the CFTR protein. Results of these studies may well point to a new drug target important in fighting the progress pulmonary disease that is a dominant clinical feature in CF.